T-Cell Marker Profiling for Anti-PD1 Response Prediction
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Solution Overview
Problem
Current methods fail to accurately predict patient response to immune checkpoint inhibitor immunotherapy, leading to ineffective treatment and potential autoimmune toxicities, necessitating a need for personalized treatment selection.
Innovation Solution
Assessing the levels of CD15s, CTLA-4, FoxP3, and Ki67 markers in specific T cell subsets before and after immunotherapy to determine responsiveness, using flow cytometry and immunological reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If immune checkpoint inhibitor therapy is administered to all cancer patients, then more patients may benefit from the treatment, but the rate of autoimmune toxicities and ineffective treatment increases
Solution Approach 1:
The patent performs preliminary assessment of T cell markers (CD15s, CTLA-4, FoxP3, Ki67) before administering immune checkpoint inhibitor therapy to predict patient responsiveness. This preliminary action identifies suitable candidates in advance, preventing unnecessary treatment and associated toxicities in non-responders while ensuring beneficial patients receive the therapy.
2Adaptability or versatility
If immune checkpoint inhibitor therapy is administered to all cancer patients, then treatment accessibility is improved, but treatment effectiveness decreases due to lack of patient selection
Solution Approach 1:
The patent implements preliminary diagnostic assessment using flow cytometry to measure T cell marker levels before therapy initiation. This enables personalized treatment selection that maintains high accessibility for identified responders while ensuring treatment effectiveness through evidence-based patient stratification.
Solution Approach 2:
The patent uses baseline T cell marker levels as predictive biomarkers to guide treatment decisions. The feedback mechanism involves comparing patient-specific marker profiles against established thresholds to determine responsiveness, enabling informed treatment selection that balances accessibility with effectiveness.
3Measurement precision
If comprehensive T cell marker assessment is performed, then prediction accuracy is improved, but diagnostic complexity and cost increase
Solution Approach 1:
The patent employs flow cytometry, a universal diagnostic platform already widely available in clinical settings, to simultaneously assess multiple T cell markers (CD15s, CTLA-4, FoxP3, Ki67) in a single test. This multi-functional approach achieves high prediction accuracy without requiring separate specialized assays for each marker, thereby limiting the increase in diagnostic complexity.
Data Source
AI summary
The present invention provides methods, systems, and kits for determining responsiveness of a subject with or susceptible to cancer to anti-PD1 immune checkpoint inhibitor immunotherapy (ICII) including determining the level of one or more of markers CD15 in CD8+Ki67/CD71+ or CD8/CD4−Ki67/CD71+ T cells, CTLA-4 in CD4+Ki67/CD71+ T cells, FoxP3 in CD4+Ki67/CD71+ T cells, Ki67 or CD71 in CD8+ T cells, wherein an increase in CD15, CTLA-4, FoxP3, or a decrease in Ki67 or CD71 prior to immunotherapy is indicative that the subject is responsive to immunotherapy, particularly PD1 ICII.